Influenza, an illness caused by respiratory infection with influenza viruses, often occurs in winter. It is known to have very high infectivity and to affect all age groups, particularly elderly people (Treanor J, 2004, N Etzgl J Med. 350(3):218-20). Influenza virus is a negative-stranded and enveloped RNA (ribonucleic acid) virus belonging to the family Orthomyxoviridae. This family has eight segments of single-stranded RNA and are classified as influenza types A, B and C. Influenza A viruses are further divided into subtypes on the basis of their major surface proteins hemagglutinin (HA) and neuraminidase (NA). Up to date, 16 HAs and 9 NAs have been identified (Cheung T K and Poon L L 2007, Ann NY Acad Sci. 1102:1-25). Influenza viruses infect a wide range of animals including birds, pigs and humans depending on their types and have a genome composed of segmented RNAs. For this reason, influenza viruses can continuously mutate and recombine, resulting in new genetic variations (Treanor J, 2004. N Engl J Med. 350(3):218-20). For this reason, it is difficult to obtain permanent immunity against influenza viruses. The most effective prevention method currently used is vaccination against particular influenza viruses expected to be prevalent.
Influenza Vaccines are generally produced using eggs, but this is an inefficient method that requires much time. Accordingly, this method has a problem in that it is difficult to produce sufficient amounts of vaccines each year within a limited time frame. To solve this problem, studies on methods of producing vaccines by cell culture are being actively conducted in several pharmaceutical companies (GSK, Baxter, etc.). In addition, it is very difficult to develop a vaccine rapidly against the pandemic influenza virus when pandemic infection occurs. Also, antiviral drugs are not completely reliable due to a problem associated with the appearance of mutant viruses having resistance.
To solve this problem, recently antibodies against influenza viruses have been actively developed for a therapeutic purpose (Throsby et al, 2008, PloS One 3 (e3942); Sui et al., 2009, Nature structural & molecular biology. 16 (265-273); Simmons et al, 2007, PloS Medicine 4 (e178)).
Blood products from recovered patients have been used to treat patients infected with various viruses, as well as to treat pandemic flu infections. For example, when patients infected with Spanish influenza virus had symptoms of pneumonia, blood products collected from patients who recovered from infection with the flu are used to treat the flu (Luke et al., 2006. Annals of internal medicine. 145:599). As such, hyperimmune globulin (IgIv) is purified from human plasma and used to treat patients infected with various viruses, but the product obtained as described above may not be safe from potential infectious agents in blood and is inefficient for mass production.
Human B cells are used for the screening of specific human monoclonal antibodies. However, immortalization of human B cells by Epstein-Barr virus (EBV) is inefficient in immortalization of B-cells and is time-consuming. To overcome this inefficiency, new techniques are being developed and used. One of these techniques is to use an RTPCR method to obtain genetic information for an antibody directly from B cells. For example, there is a method comprising staining B cells that express an antibody to a specific antigen, isolating the B cells using a FACS sorter, obtaining genetic information for the antibody from the single B cells by an RT-PCR method, inserting the genetic information into an expression vector, and transfecting the expression vector into animal cells, thereby producing a large amount of the antibody. To perform such a production in an easier and rapid manner, the following technique can be used. The new technique “immunospot array assay on a chip” (ISAAC) enables an antibody gene to be obtained by screening single B cells, which secrete a specific monoclonal antibody, within several weeks (Jin et al., 2009 Nat Med. 15, 1088-1092). The antibody thus obtained is a natural human antibody which can be more effective in terms of immunogenic issues.